==== Front Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.39788 Internal Medicine Neurology Psychiatry Association of Migraine Headache With Depression, Anxiety, and Stress in the Population of Makkah City, Saudi Arabia: A Cross-Sectional Study Muacevic Alexander Adler John R Babateen Omar 1 Althobaiti Fadi S 2 Alhazmi Mohannad A 2 Al-Ghamdi Eyad 2 Alharbi Faeqah 2 Moffareh Alshaymaa K 2 Matar Fay M 2 Tawakul Abdullah 2 Samkari Jamil A 3 1 Department of Physiology, Umm Al-Qura University, Makkah, SAU 2 Department of Medicine, Umm Al-Qura University, Makkah, SAU 3 Department of Family and Community Medicine, King Abdulaziz University, Faculty of Medicine, Jeddah, SAU Fadi S. Althobaiti fadithobaiti@gmail.com 31 5 2023 5 2023 15 5 e3978831 5 2023 Copyright © 2023, Babateen et al. 2023 Babateen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from https://www.cureus.com/articles/159256-association-of-migraine-headache-with-depression-anxiety-and-stress-in-the-population-of-makkah-city-saudi-arabia-a-cross-sectional-study Introduction Migraine is characterized by persistent headaches and a wide range of symptoms, such as nausea, vomiting, and photophobia. The chance of developing a chronic migraine might be increased by lifestyle variables like obesity, stress, and excessive medication use. According to previous studies in Saudi Arabia, migraines are more common there than they are globally. The study aimed to examine the migraine associations with depression, anxiety, and stress in the population of Makkah City, Saudi Arabia. Methods The study employed a descriptive cross-sectional design with a non-probability snowball sampling technique and an online questionnaire that included sociodemographic characteristics, the International Classification of Headache Disorders-3 (ICHD-3) criteria for migraine assessment, and the Depression, Anxiety, and Stress Scale-21 (DASS-21) measure for depression, anxiety, and stress. Results Our study included 418 participants, out of whom 73.7% were female and 26.3% were male. Regarding migraine, only 8.9% of participants met the ICHD-3 criteria for migraine headache screening, with a female predominance (78.4%). The study showed a high prevalence of depression, anxiety, and stress among the population (63.9%, 63.6%, and 55%, respectively), with females having a higher prevalence. Depression, anxiety, and stress had an equal prevalence of 78.4% among migraineurs, which was significantly higher than that of non-migraineurs. Conclusions The study found significant associations between migraine and depression, anxiety, and stress. This study provides insights into the association between these conditions. The study's findings suggest the need for screening and management of mental health conditions in patients with migraine. However, extensive efforts are needed to be applied in different cities and demographics for a more precise understanding of the association. ichd-3 dass-21 stress anxiety depression association saudi arabia makkah city cross sectional migraine ==== Body pmcIntroduction Migraine is a primary headache disorder characterized by recurrent attacks of mostly unilateral headaches that are frequently accompanied by nausea, vomiting, and light sensitivity [1]. It is caused by the activation of a deep-brain mechanism that results in the production of pain-inducing inflammatory substances around the head's nerves and blood vessels [2]. Migraines are classified into two types: migraine with aura (MA) and migraine without aura (MO) [3]. Lifestyle-related factors can significantly increase the likelihood of developing migraines and the consequences on the quality of life (QoL). The most important modifiable risk factors for chronic migraine include overuse of acute migraine medication, depression, obesity, and stressful life. In addition, age, female gender, and low educational status are non-modifiable risk factors that increase the risk of chronic migraine [4]. It could be avoided if environmental, nutritional, and behavioral triggers were identified and managed [5]. According to the Global Burden of Disease (GBD), headache disorders are the most prevalent and disabling diseases worldwide. The global prevalence of active headache disorders was 52.0%, of which migraine accounted for 14.0% of these cases [6]. The prevalence of migraine in Saudi Arabia is considerably higher than global averages [7]. A local study has reported the prevalence of migraine headaches to be 37.2%, with a higher prevalence among females (81.1%) and the highest prevalence observed among students (43.3%) [8]. Speaking of mortality, migraine headaches are unlikely to cause death directly. However, due to a higher risk of cardiovascular events, mortality rates were higher in women with migraine with aura [9]. A recent study conducted in Saudi Arabia reported prevalence data for depression, anxiety, and stress among the general population and found a depression prevalence of 28.9%, an anxiety prevalence of 16.4%, and a stress prevalence of 11.9% [10]. In a cross-sectional observational study conducted by Pearl et al. on 567 predominantly female (87.3%) migraine patients, they found a positive correlation between the patient’s Migraine Disability Assessment Scale (MIDAS) and their Patient Health Questionnaire 2 (PHQ-2) [11]. AlQarni et al. conducted a descriptive cross-sectional survey in the Aseer region of Saudi Arabia on 1123 adults, of whom 152 (13.5%) reported no headache, 833 (74.2%) had non-migraine headaches (NMH), and 138 (12.3%) had migraine headaches, depression was reported in 26.1% of migraine patients, compared to 10.9% and 6.6% in NMH cases and adults with no headache, respectively [12]. Another study, conducted in Saudi Arabia, assessed 247 migraine patients aged between 16 and 45 years using the Depression Anxiety Stress Scale (DASS-21) questionnaire and found that 73.3% of the patients met the criteria for anxiety, while 70.9% and 72.3% of patients met the criteria for depression and stress, respectively [13]. Furthermore, a study on 1340 female students at Taif University in Saudi Arabia found that 32.5% of them have migraines and report the main triggers for migraines and stress and anxiety. The study also reported that 51.8% of migraine students were depressed [14]. Additionally, a study conducted in 2012 that aimed to assess the role of depression in migraine chronification concluded that depression is a significant predictor of migraine chronicity [15]. As per the author's knowledge, this was the first study conducted to assess the relationship between migraine headaches and anxiety, depression, and stress in Makkah City, Saudi Arabia, while only a few studies have been conducted worldwide. Therefore, the study aimed to increase understanding of the association of migraine headaches with depression, anxiety, and stress among the population of Makkah City, Saudi Arabia, and to develop more effective strategies for managing these conditions in this specific cultural and environmental context. Materials and methods Study design The study employed a descriptive cross-sectional study design with a non-probability snowball sampling technique as the sampling method. An online questionnaire (in Arabic) consisting of three parts was used for sociodemographic characteristics (Appendix). In addition, the International Classification of Headache Disorders (ICHD-3) criteria for migraine assessment and the DASS-21 measured the association between depression, anxiety, and stress in migraine patients [16,17]. The questionnaire was transferred to Google Forms and administered electronically to participants via social media platforms. Study population The study's target population was general Arabic and English-speaking adults living in Makkah, Saudi Arabia. This study excluded participants who failed to complete the questionnaire, lived outside of Makkah City, and spoke neither Arabic nor English language. Sampling methodology The survey was conducted among the general public in Makkah City, Saudi Arabia, from February 26 to April 1, 2023. A written consent form was obtained from all participants before they filled out the questionnaire. According to OpenEpi version 3.1, a sample size of at least 384 participants was considered for a confidence interval level of 95%, an anticipated percentage of frequency of 50%, and a design effect of 1. The questionnaire consisted of three parts and was written in Arabic and English languages. The first part of the questionnaire included sociodemographic characteristics, such as age, gender, nationality, marital status, level of education, occupation, and income. The second part consisted of ICHD-3 migraine criteria. Following that, participants were asked to complete the third part of the questionnaire, which consists of DASS-21 to assess the presence of depression, anxiety, and stress. The anonymity of survey respondents was maintained, and their personal information, such as name, address, phone number, or email address, was not collected in electronic data collection forms; the data were automatically entered into an Excel spreadsheet. After verification and filtering, the data were transferred to BlueSky Statistics version 10.2.1 (Chicago, IL: BlueSky Statistics LLC) for analysis. Data analysis Data were extracted, reviewed, coded, and entered into BlueSky Statistics version 10.2.1 statistical software. The results were presented as frequencies and percentages. Descriptive statistics were obtained for all sociodemographic variables, including participants' age in years, gender, nationality, marital status, education level, occupation, and family monthly income in Saudi Riyal (SAR), and analysis based on frequency and percent distribution was performed for these sociodemographic variables. Migraine prevalence was estimated using ICHD-3 criteria, and the symptoms' frequencies and percentages were plotted in a graph. As for DASS-21, frequency and percentage were tabulated for depression, anxiety, and stress with the following different levels: normal, mild, moderate, severe, and extremely severe for all participants. The chi-square test was used to assess the association between demographics and migraine, demographics and depression, anxiety and stress, and lastly, depression, anxiety, and stress with migraine. A significant association was determined by a p-value of <0.05. Ethical part and confidentiality Consent was obtained from each participant through the questionnaire. The aims of the research were stated in the questionnaire form for all participants. Additionally, all participants' identities were kept anonymous and confidential. The responses were only accessible to the investigators. Ethical approval was obtained from the Biomedical Ethics Committee of Umm Alqura University (UQU) (#HAPO-02-K-012-2023-02-1476). Results A total of 567 individuals participated in the study. One participant was excluded considering he was under the age of 18 years, and 148 were excluded because they lived outside of Makkah City, leaving the included sample size at 418. The sociodemographic data in Table 1 show that the sample is predominantly female - 308 (73.7%), with only 110 (26.3%) males. The participants’ ages ranged from 18 to 55 years, with the majority of the participants ranging in age from 18 to 25 years (46.9%). A total of 393 participants were Saudis (94%), of which 318 had a university-level education (76.1%). Around 50.2% of them were single, and 46.2% were married. Table 1 Sociodemographic characteristics of participants. Variables Demographic data n=418 % Gender Male 110 26.3% Female 308 73.7% Age (years) 18-25 196 46.9% 26-35 38 9.1% 36-45 71 17.0% 46-55 88 21.1% >55 25 6.0% Nationality Saudi 393 94.0% Non-Saudi 25 6.0% Marital status Single 210 50.2% Married 193 46.2% Divorced 10 2.4% Widowed 5 1.2% Education level Primary 1 0.2% Intermediate 5 1.2% Secondary 66 15.8% University 318 76.1% Postgraduate 28 6.7% Occupation Student 181 43.3% Professional 149 35.6% Self-employed 17 4.1% Retired 25 6.0% Housewife 37 8.9% Unemployed 9 2.2% Family monthly income 0-5,000 84 20.1% 5,001-10,000 86 20.6% 10,001-15,000 99 23.7% 15,000-20,000 81 19.4% >20,000 68 16.3% Figure 1 shows that only 37 (8.9%) of the 418 participants met the ICHD-3 criteria for migraine headache screening. A pulsating headache was the most frequently reported symptom, as shown in Figure 2, followed by photophobia and phonophobia (83.8% and 81.1%), followed by nausea and/or vomiting at 70.3%. Moderate-to-severe headaches were reported in 64.9% of participants, and 50% of them reported that their headache was unilateral. Figure 1 Prevalence of migraine in participants. Figure 2 Frequency of migraine symptoms. Depression prevalence results are presented in Table 2. It indicates that approximately a third of the 151 participants (36.1%) showed no signs of depression. A total of 50 participants (12%) reported mild depression, which is followed by moderate depression, reported in 82 (19.6%), severe depression in 49 (11.7%), and extremely severe depression in 86 (20.6%). In terms of anxiety, 152 (36.4%) participants were unaffected by anxiety, while 28 (6.7%) had mild anxiety, 80 (19.1%) had moderate anxiety, 47 (11.2%) complained of severe anxiety, and lastly, an alarming 111 (26.5%) participants suffered from extremely severe anxiety. In the context of stress, 188 (45%) were normal. A total of 46 (11%) participants had mild stress, 70 (16.7%) complained of moderate stress, 62 (14.8%) suffered from severe stress, and 52 (12.4%) reported extremely severe levels of stress. Table 2 Prevalence of depression, anxiety, and stress. Variables n=418 % Depression Normal 151 36.1% Mild 50 12.0% Moderate 82 19.6% Severe 49 11.7% Extremely severe 86 20.6% Anxiety Normal 152 36.4% Mild 28 6.7% Moderate 80 19.1% Severe 47 11.2% Extremely severe 111 26.5% Stress Normal 188 45.0% Mild 46 11.0% Moderate 70 16.7% Severe 62 14.8% Extremely severe 52 12.4% Table 3 shows that females had a higher prevalence of migraine than males, with 29 (9.4%) females and eight (7.3%) males. The prevalence rates for age groups 36-45 and 18-25 were eight (11.3%) and 22 (11.2%), respectively. Participants aged 46-55 years scored the lowest prevalence of migraine at 3.4%. No sociodemographic variable was significantly associated with migraine. Table 3 Association between migraine headache and sociodemographic variables. Variables Without migraine With migraine p-Value n % n % Gender Male 102 92.7% 8 7.3% 0.5 Female 279 90.6% 29 9.4% Age (years) 18-25 174 88.8% 22 11.2% 0.2 26-35 35 92.1% 3 7.9% 36-45 63 88.7% 8 11.3% 46-55 85 96.6% 3 3.4% >55 24 96.0% 1 4.0% Nationality Saudi 358 91.1% 35 8.9% 0.9 Non-Saudi 23 92.0% 2 8.0% Marital status Single 187 89.0% 23 11.0% 0.4 Married 180 93.3% 13 6.7% Divorced 9 90.0% 1 10.0% Widowed 5 100% 0 0% Education level Primary 1 100% 0 0% 0.6 Intermediate 5 100% 0 0% Secondary 63 95.5% 3 4.5% University 287 90.3% 31 9.7% Postgraduate 25 89.3% 3 10.7% Occupation Student 161 89.0% 20 11.0% 0.4 Professional 135 90.6% 14 9.4% Self-employed 17 100% 0 0% Retired 24 96.0% 1 4.0% Housewife 36 97.3% 1 2.7% Unemployed 8 88.9% 1 11.1% Family monthly income 0-5,000 78 92.9 6 7.1% 0.6 5,001-10,000 76 88.4% 10 11.6% 10,001-15,000 88 88.9% 11 11.1% 15,000-20,000 76 93.8% 5 6.2% >20,000 63 92.4% 5 7.4% As shown in Table 4, females had a depression prevalence rate of 67.3% (207), of which the mild, moderate, severe, and extremely severe depression prevalence rates were 11.7% (36), 21.1% (65), 10.1% (31), and 24.4% (75), respectively. Depression prevalence was highest among those aged 18-25 years (71.4%), followed by adults aged 26-35 years (68.4%). Participants aged 55 years and above had the lowest prevalence of depression (36%). Single participants showed a higher prevalence of depression (72.9%), followed by divorced participants (70%) when compared to married participants (54.9%). Participants with family monthly income of 0-5,000 (SAR) scored the highest prevalence of depression at 76.2%, followed by participants with family monthly income of >20,000 (SAR) and 15,001-20,000 (SAR) at 64.7% and 64.2%, respectively, while the lowest rate of prevalence was among those with family monthly income of 10,001-15,000 (SAR) at 54.5%. The only significant variables in the association between depression and sociodemographic data were gender (p=0.003), marital status (p=0.033), and monthly family income (p=0.0049). Table 4 Association between depression and sociodemographic variables. *P-value<0.01 is statistically highly significant. **P-value<0.05 is statistically significant. Variables Depression scale p-Value Normal Mild Moderate Severe Extremely severe Gender Female n 101 36 65 31 75 0.003* % 32.8% 11.7% 21.1% 10.1% 24.4% Male n 50 14 17 18 11 % 45.5% 12.7% 15.5% 16.4% 10.0% Age (years) >55 n 16 1 5 1 2 0.18 % 64.0% 4.0% 20.0% 4.0% 8.0% 18-25 n 56 26 38 28 48 % 28.6% 13.3% 19.4% 14.3% 24.5% 26-35 n 12 4 8 5 9 % 31.6% 10.5% 21.1% 13.2% 23.7% 36-45 n 29 8 15 5 14 % 40.8% 11.3% 21.1% 7.0% 19.7% 46-55 n 38 11 16 10 13 % 43.2% 12.5% 18.2% 11.4% 14.8% Nationality Non-Saudi n 8 3 5 4 5 0.97 % 32.0% 12.0% 20.0% 16.0% 20.0% Saudi n 143 47 77 45 81 % 36.4% 12.0% 19.6% 11.5% 20.6% Total n 151 50 82 49 86 Marital status Divorced n 3 1 1 2 3 0.033** % 30.0% 10.0% 10.0% 20.0% 30.0% Married n 87 21 37 18 30 % 45.1% 10.9% 19.2% 9.3% 15.5% Single n 57 28 43 29 53 % 27.1% 13.3% 20.5% 13.8% 25.2% Widowed n 4 0 1 0 0 % 80.0% 0 20.0% 0 0 Total n 151 50 82 49 86 Educational level Intermediate n 2 1 1 0 1 0.49 % 40.0% 20.0% 20.0% 0 20.0% Postgraduate n 12 1 7 3 5 % 42.9% 3.6% 25.0% 10.7% 17.9% Primary n 0 0 0 1 0 % 0 0 0 100.0% 0 Secondary n 17 8 17 8 16 % 25.8% 12.1% 25.8% 12.1% 24.2% University n 120 40 57 37 64 % 37.7% 12.6% 17.9% 11.6% 20.1% Total n 151 50 82 49 86 Occupation Housewife n 15 3 5 5 9 0.12 % 40.5% 8.1% 13.5% 13.5% 24.3% Professional n 62 17 34 12 24 % 41.6% 11.4% 22.8% 8.1% 16.1% Retired n 15 0 3 3 4 % 60.0% 0 12.0% 12.0% 16.0% Self-employed n 3 4 3 4 3 % 17.6% 23.5% 17.6% 23.5% 17.6% Student n 53 26 34 24 44 % 29.3% 14.4% 18.8% 13.3% 24.3% Unemployed n 3 0 3 1 2 % 33.3% 0.0 33.3% 11.1% 22.2% Family monthly income >20,000 n 24 6 14 12 12 0.0049* % 35.3% 8.8% 20.6% 17.6% 17.6% 0-5,000 n 20 11 28 8 17 % 23.8% 13.1% 33.3% 9.5% 20.2% 10,001-15,000 n 45 11 14 4 25 % 45.5% 11.1% 14.1% 4.0% 25.3% 15,000-20,000 n 29 11 10 17 14 % 35.8% 13.6% 12.3% 21.0% 17.3% 5001-10000 n 33 11 16 8 18 % 38.4% 12.8% 18.6% 9.3% 20.9% Table 5 shows that 212 (68.8%) female participants reported anxiety, with 20 (6.5%) suffering from mild anxiety, 62 (20.1%) moderate anxiety, 37 (12%) severe anxiety, and 93 (30.2%) suffering from extremely severe anxiety. Participants aged 26-35 years scored the highest levels of anxiety (71.1%), while participants over the age of 55 years scored the lowest prevalence of anxiety (44%). A total of 251 (63.9%) Saudi participants were affected by anxiety compared to non-Saudi participants, who had a prevalence of 15 (60%). Gender was the only sociodemographic variable with a significant association (p=0.0033) with anxiety. Table 5 Association between anxiety and sociodemographic variables. *P-value<0.01 is statistically highly significant. Variables Anxiety scale p-Value Normal Mild Moderate Severe Extremely severe Gender Female n 96 20 62 37 93 0.0033* % 31.2% 6.5% 20.1% 12.0% 30.2% Male n 56 8 18 10 18 % 50.9% 7.3% 16.4% 9.1% 16.4% Age (years) >55 n 14 1 4 3 3 0.24 % 56.0% 4.0% 16.0% 12.0% 12.0% 18-25 n 58 13 46 23 56 % 29.6% 6.6% 23.5% 11.7% 28.6% 26-35 n 11 2 6 7 12 % 28.9% 5.3% 15.8% 18.4% 31.6% 36-45 n 31 4 9 6 21 % 43.7% 5.6% 12.7% 8.5% 29.6% 46-55 n 38 8 15 8 19 % 43.2% 9.1% 17.0% 9.1% 21.6% Nationality Non-Saudi n 10 1 4 4 6 0.89 % 40.0% 4.0% 16.0% 16.0% 24.0% Saudi n 142 27 76 43 105 % 36.1% 6.9% 19.3% 10.9% 26.7% Marital status Divorced n 4 0 1 0 5 0.138 % 40.0% 0 10.0% 0 50.0% Married n 85 13 30 20 45 % 44.0% 6.7% 15.5% 10.4% 23.3% Single n 60 15 48 27 60 % 28.6% 7.1% 22.9% 12.9% 28.6% Widowed n 3 0 1 0 1 % 60.0% 0 20.0% 0 20.0% Educational level Intermediate n 1 1 2 0 1 0.577 % 20.0% 20.0% 40.0% 0 20.0% Postgraduate n 13 1 5 3 6 % 46.4% 3.6% 17.9% 10.7% 21.4% Primary n 0 0 1 0 0 % 0 0 100.0% 0 0 Secondary n 20 3 11 12 20 % 30.3% 4.5% 16.7% 18.2% 30.3% University n 118 23 61 32 84 % 37.1% 7.2% 19.2% 10.1% 26.4% Occupation Housewife n 14 1 5 5 12 0.594 % 37.8% 2.7% 13.5% 13.5% 32.4% Professional n 63 10 23 15 38 % 42.3% 6.7% 15.4% 10.1% 25.5% Retired n 12 2 2 5 4 % 48.0% 8.0% 8.0% 20.0% 16.0% Self-employed n 5 1 4 3 4 % 29.4% 5.9% 23.5% 17.6% 23.5% Student n 54 13 45 18 51 % 29.8% 7.2% 24.9% 9.9% 28.2% Unemployed n 4 1 1 1 2 % 44.4% 11.1% 11.1% 11.1% 22.2% Family monthly income >20,000 n 28 3 12 7 18 0.73 % 41.2% 4.4% 17.6% 10.3% 26.5% 0-5,000 n 26 3 16 13 26 % 31.0% 3.6% 19.0% 15.5% 31.0% 10,001-15,000 n 35 6 24 11 23 % 35.4% 6.1% 24.2% 11.1% 23.2% 15,000-20,000 n 30 10 14 8 19 % 37.0% 12.3% 17.3% 9.9% 23.5% 5,001-10,000 n 33 6 14 8 25 % 38.4% 7.0% 16.3% 9.3% 29.1% The prevalence of stress is shown in Table 6 for females at 180 (58.4%) and 50 (45.5%) for males. Participants aged 18-25 years had the highest prevalence out of all the age groups at 123 (65.8%), while participants over 55 years had the lowest prevalence at six (24%). Divorced participants had a higher prevalence (70%) when compared to married and single participants, 85 (44%), and 137 (65.2%), respectively. Out of all the demographic data, only gender (p=0.0087) and marital status (p=0.0074) had significant associations with stress. Table 6 Association between stress and sociodemographic variables. *P-value<0.01 is statistically highly significant. Variables Stress scale p-Value Normal Mild Moderate Severe Extremely Severe Gender Female n 128 35 47 53 45 0.0087* % 41.6% 11.4% 15.3% 17.2% 14.6% Male n 60 11 23 9 7 % 54.5% 10.0% 20.9% 8.2% 6.4% Age (years) >55 n 19 1 3 0 2 0.074 % 76.0% 4.0% 12.0% 0 8.0% 18-25 n 73 25 38 32 28 % 37.2% 12.8% 19.4% 16.3% 14.3% 26-35 n 13 5 7 9 4 % 34.2% 13.2% 18.4% 23.7% 10.5% 36-45 n 36 8 7 11 9 % 50.7% 11.3% 9.9% 15.5% 12.7% 46-55 n 47 7 15 10 9 % 53.4% 8.0% 17.0% 11.4% 10.2% Nationality Non-Saudi n 14 3 2 2 4 0.55 % 56.0% 12.0% 8.0% 8.0% 16.0% Saudi n 174 43 68 60 48 % 44.3% 10.9% 17.3% 15.3% 12.2% Marital status Divorced n 3 0 3 1 3 0.0074* % 30.0% 0 30.0% 10.0% 30.0% Married n 108 17 26 23 19 % 56.0% 8.8% 13.5% 11.9% 9.8% Single n 73 29 40 38 30 % 34.8% 13.8% 19.0% 18.1% 14.3% Widowed n 4 0 1 0 0 % 80.0% 0 20.0% 0 0 Educational Level Intermediate n 2 1 0 1 1 0.353 % 40.0% 20.0% 0 20.0% 20.0% Postgraduate n 12 3 5 3 5 % 42.9% 10.7% 17.9% 10.7% 17.9% Primary n 0 0 1 0 0 % 0 0 100.0% 0 0 Secondary n 25 10 17 11 3 % 37.9% 15.2% 25.8% 16.7% 4.5% University n 149 32 47 47 43 % 46.9% 10.1% 14.8% 14.8% 13.5% Occupation Housewife n 15 6 7 6 3 0.2 % 40.5% 16.2% 18.9% 16.2% 8.1% Professional n 83 11 19 19 17 % 55.7% 7.4% 12.8% 12.8% 11.4% Retired n 13 2 6 2 2 % 52.0% 8.0% 24.0% 8.0% 8.0% Self-employed n 7 1 5 1 3 % 41.2% 5.9% 29.4% 5.9% 17.6% Student n 67 25 30 34 25 % 37.0% 13.8% 16.6% 18.8% 13.8% Unemployed n 3 1 3 0 2 % 33.3% 11.1% 33.3% 0 22.2% Family monthly income >20,000 n 25 7 16 12 8 0.38 % 36.8% 10.3% 23.5% 17.6% 11.8% 0-5,000 n 34 12 15 12 11 % 40.5% 14.3% 17.9% 14.3% 13.1% 10,001-15,000 n 51 8 14 10 16 % 51.5% 8.1% 14.1% 10.1% 16.2% 15,000-20,000 n 39 5 16 13 8 % 48.1% 6.2% 19.8% 16.0% 9.9% 5,001-10000 n 39 14 9 15 9 % 45.3% 16.3% 10.5% 17.4% 10.5% As indicated in Table 7, the prevalence of mild, moderate, severe, and extremely severe depression in respondents suffering from migraines was two (5.4%), eight (21.6%), five (13.5%), and 14 (37.8%), respectively, when compared to non-migraineurs, who had a prevalence of 48 (12.6%), 74 (19.4%), 44 (11.5%), and 72 (18.9%), respectively. When it comes to anxiety, migraineurs reported no mild anxiety but a higher prevalence of moderate anxiety (5, 13.5%), severe anxiety (3, 8.1%), and extremely severe anxiety (21, 56.8%), when compared to non-migraineurs, they reported a prevalence of mild anxiety (28, 7.3%), moderate anxiety (75, 19.7%), severe anxiety (44, 11.5%), and extremely severe anxiety (90, 23.6%). Finally, there was an increased prevalence of stress among migraineurs, with three (8.1%) reporting mild stress, eight (21.6%) having moderate stress, four (10.8%) reporting severe stress, and 14 (37.8%) reporting extremely severe stress, where non-migraineurs reported mild, moderate, severe, and extremely severe stress of 43 (11.3%), 62 (16.3%), 58 (15.2%), and 38 (10%). Depression, anxiety, and stress were all found to be significantly associated with migraines (p=0.04, p=0.0005, and p=0.00002, respectively). Table 7 Association between migraine and depression, anxiety, and stress. *P-value<0.05 is statistically significant. **P-value<0.01 is statistically highly significant. Variables Depression scale p-Value Normal Mild depression Moderate depression Severe depression Extremely severe depression Migraine status Migraine n 8 2 8 5 14 0.04* % 21.6% 5.4% 21.6% 13.5% 37.8% Non-migraine n 143 48 74 44 72 % 37.5% 12.6% 19.4% 11.5% 18.9% Migraine n 8 0 5 3 21 0.0005** % 21.6% 0 13.5% 8.1% 56.8% Non-migraine n 144 28 75 44 90 % 37.8% 7.3% 19.7% 11.5% 23.6% Migraine n 8 3 8 4 14 0.00002** % 21.6% 8.1% 21.6% 10.8% 37.8% Non-migraine n 180 43 62 58 38 % 47.2% 11.3% 16.3% 15.2% 10.0% Discussion The purpose of this cross-sectional study was to determine the relationship between migraine headaches and depression, anxiety, and stress in the Makkah City, Saudi Arabia, population. Our study findings revealed that only 8.9% of the study participants reported experiencing migraines. The study's migraine prevalence is lower than the global prevalence of 14% [6]. This contradicts the findings of a previous study, which concluded that migraine prevalence in Saudi Arabia is higher than the global average [7]. The most reported symptom was a pulsating headache, followed by photophobia, phonophobia, nausea, and vomiting. A higher prevalence result was reported for the female gender, which was also consistent with findings reported in a previously published study [11-13]. This gender difference can be explained by the fluctuations in estrogen and progesterone, which have been associated with migraine pathogenesis [18]. The number of participants who reported normal scores regarding depression was 151 (36.1%), 152 (36.4%), and 188 (45%) for anxiety and stress. A larger proportion of participants (63.9%) reported mild, moderate, severe, or extremely severe depression, which is also found to be an alarming increase in prevalence when compared with a previous 2021 study conducted in the city of Jeddah, Saudi Arabia, studying the prevalence of migraine and its effect on QoL among the general population that concluded a depression prevalence of 37.2% [8]. In the current study, the reports of mild, moderate, severe, or extremely severe anxiety were (63.6%), and the reports of mild, moderate, severe, and extremely severe stress were (55%). The results indicate an increase in prevalence when compared to the findings of a recent 2020 study in Saudi Arabia that aimed to study the prevalence of depression, anxiety, and stress among the general population and found an anxiety prevalence of 16.4% and a stress prevalence of 11.9%. This difference could be attributed to the variation in sample demographic characteristics [10]. The findings of the current study reported that gender was significantly associated with depression, anxiety, and stress, with females being more susceptible to all of them. Additionally, depression and stress were strongly associated with marital status, with singles and divorcees being more susceptible. Despite female susceptibility to depression, anxiety, and stress, a recent 2021 study in the region demonstrated an insignificant association between gender and marital status (p>0.05) [13]. Our study found that depression, anxiety, and stress were all significantly associated with migraine, with an equally high prevalence of 78.4% among migraineurs. This is consistent with a previous study conducted among migraine patients in Saudi Arabia, which found abnormal scores for depression (70.9%), anxiety (73.3%), and stress (72.3%) [13]. Another 2020 study conducted in North America studied the impact of depression and anxiety symptoms in migraineurs and found a corresponding percentage of anxiety prevalence (75.3%), but the prevalence of depression was significantly lower (18%) [11]. The bidirectional relationship between depression and migraine has been observed in previous studies, with depression being a strong predictor of the progression of migraine [15]. However, the exact mechanism underlying this association is unclear, but one hypothesis suggests that it may be due to low levels of 5-hydroxytryptamine (5-HT) or serotonin receptors [19]. As for anxiety, a study conducted in Taif City reported anxiety as one of the main triggers for migraine attacks [14]. Another study conducted in Jeddah also found that stress and anxiety accounted for 81.6% of the observed triggering factors for migraines [8]. Furthermore, stress was identified as a migraine trigger in the Taif City study [14]. The concurrent presence of depression, anxiety, and stress with migraine can significantly affect the QoL of affected individuals. We recommend screening patients with migraines for the presence or development of these mental health conditions, as well as the need to manage them effectively. It is critical to prevent the development of anxiety disorders and depression in migraine patients, which can be accomplished by reducing the number of headache episodes with effective prophylactic pharmacotherapy. We also recommend that further studies be conducted to better understand the relationship between migraine and these mental health disorders in order to develop a more coordinated and direct approach to aid in the diagnosis and management of these conditions. Limitations Despite making an effort to obtain accurate, precise, and representative outcomes, this study encountered certain limitations. Firstly, collecting data using an online questionnaire has inherent limitations. Second, the majority of the respondents were female (73.7%), Saudi (94.0%), and had a university-level education (76.1%). Another limitation is that the migraine prevalence in the study sample is relatively small (8.9%). These factors may have resulted in unintended biases in the findings. It is important to consider these limitations when interpreting the results of the study and to use caution when generalizing the findings to other populations or contexts. Nonetheless, this study provides insight into the current situation and confirms the outcomes of previous global and local research on the subject. The study used standardized measures to assess migraine headaches, depression, anxiety, and stress, which increases the reliability and validity of the study findings. More research in this area is required, using different methodologies, focusing on different sociodemographic characteristics, and exploring other unexplored regions of Saudi Arabia. Conclusions Our study provides valuable insights into the association between migraine and depression, anxiety, and stress in the population of Makkah City. The findings highlight the importance of screening and effective management of mental health conditions in patients with migraine to improve their QoL, as the results showed a significant association between migraine and depression, anxiety, and stress. Further studies with a larger sample are warranted in different cities and demographics to better understand the relationship between these conditions and develop more effective interventions. All authors contributed equally and should be considered joint-first authors of this study. The authors would like to extend their special thanks to the data collectors for this research, Ibrahim Klantan, Enad Alkhdidi, Asmaa Almalki, Renad Alotaibi, and Hadhyah Alabdali. Participant data that has been anonymized are stored. Data may be acquired from Fadi S. Althobaiti (fadithobaiti@gmail.com) on reasonable request. Human Ethics Animal Ethics Appendices علاقة الصداع النصفي مع الاكتئاب والقلق والتوتر بين البالغين في مدينة مكة المكرمة، المملكة العربية السعودية: دراسة مقطعية. Association of Migraine Headache with Depression, Anxiety, and Stress in the Population of Makkah City, Saudi Arabia: A Cross-Sectional Study (English translation) ندعوكم للمشاركة في هذا الاستبيان المقدم من فريق بحثي يهدف الى قياس علاقة الشقيقة وارتباطها مع الإكتئاب والقلق والتوتر عند البالغين في مدينة مكة المكرمة في المملكة العربية السعودية. المشاركة في هذه الدراسة تطوعية و جميع المعلومات سيتم التعامل معها بكامل السرية واستخدامها لأهداف بحثية فقط. لن يتم نشر أي معلومات شخصية، في حال الموافقة للمشاركة في هذا الاستيبان الرجاء إكماله وارساله عند الإنتهاء منه. شاكرين حسن تعاونكم. This questionnaire is conducted by a research team that aims to measure the association of migraine headache with depression, anxiety, and stress in Makkah City. All information will be treated with complete confidentiality and used for research purposes only. No personal information will be published. If you agree to participate in our study, please complete and send the following questionnaire. Thank you for your contribution (English translation). Table 8 Sociodemographic characteristics. Question Answers الجنس Gender ذكر Male أنثى Female العمر Age (years) <18 18-25 26-35 36-45 46-55 >55 الجنسية Nationality سعودي Saudi غير سعودي Non-Saudi مدينة السكن City of residence مكة المكرمة Makkah أخرى Other الحالة الإجتماعية Marital status أعزب Single متزوج Married مطلق Divorced أرمل Widowed المستوى الدراسي Education level ابتدائي Primary متوسط Intermediate ثانوي Secondary جامعي University دراسات عليا Postgraduate الوظيفة Occupation طالب Student موظف Professional مهنة حرة Self-employed متقاعد Retired ربة منزل Housewife غير موظف Unemployed دخل العائلة الشهري (بالريال السعودي) Family monthly income (In Saudi Riyal) 0-5,000 5,001-10,000 10,001-15,000 15,001-20,000 >20,000 Table 9 ICHD-3 criteria for migraine without aura. ICHD-3: International Classification of Headache Disorders-3 Question Answers عادة ما أواجه نوبات صداع تستمر بين ٤-٧٢ ساعة عند عدم علاجها؟ I have experienced headache attacks lasting 4-72 hours (untreated or unsuccessfully treated). Yes No كم مرة واجهت هذه النوبة؟ How many times have you experienced the attacks? أقل من ٥ مرات Less than 5 attacks أكثر من ٥ مرات More than 5 attacks لم أمر بهذه النوبة من قبل I have not experienced any attacks خصائص الصداع الذي يواجهني هي كالتالي (تستطيع إختيار أكثر من إجابة) Headache is characterized by (you can choose multiple answers) صداع مقتصر على منتصف الرأس Unilateral location طبيعة الصداع نابضة Pulsating quality أستطيع وصف شدة الألم من متوسطة إلى شديدة Moderate-to-severe pain intensity تزداد حدة الصداع مع ممارسة النشاطات البدنية مما يؤدي إلى تجنبها في فترة نوبة الصداع Aggravation by or causing avoidance of routine physical activity لا أواجه أي مما سبق None of the above أواجه الأعراض التالية أثناء نوبة الصداع During headache attacks, I have experienced غثيان أو إستفراغ Nausea and/or vomiting حساسية تجاه الأصوات أو الإضاءة Photophobia and phonophobia لا أواجه أي مما سبق None of the above كم مرة واجهت أحد الأعراض السابقة أثناء نوبة الصداع؟ How many times have you experienced the previous symptoms during a headache attack? أقل من ٥ مرات Less than 5 attacks أكثر من ٥ مرات More than 5 attacks لم أمر بهذه النوبة من قبل I have not experienced any symptoms مقياس الإكتئاب، والقلق، والتوتر: أقرأ كل من النصوص التالية ثم ضع علامة على الرقم (٠، ١، ٢، أو ٣) الذي يبين درجة إنطباق هذا الشعور عليك في الأسبوع الماضي، لا يوجد إجابات صحيحة أو خاطئة، لا تقضي وقتًا طويلًا في أي منها. استعمل التقديرات التالية عند الإجابة: ٠) لا ينطبق علي بتاتًا. ١) ينطبق علي بعض الشيء أو قليلًا من الأوقات. ٢) ينطبق علي بدرجة ملحوظة أو بعض الأوقات. ٣) ينطبق علي كثيرًا جدًا، أو معظم الأوقات. DASS-21 questionnaire (English translation): Please read each statement and circle a number (0, 1, 2, or 3) that indicates how much the statement applied to you over the past week. There are no right or wrong answers. Do not spend too much time on any statement. The rating scale is as follows: 0 - did not apply to me at all. 1 - Applied to me to some degree, or some of the time. 2 - Applied to me to a considerable degree or a good part of time. 3 - Applied to me very much or most of the time. Table 10 Depression, Anxiety, and Stress Scale-21 (DASS-21) questionnaire. وجدت صعوبة في الاسترخاء والراحة. I found it hard to wind down. 0 1 2 3 شعرت بجفاف في حلقي. I was aware of dryness of my mouth. 0 1 2 3 لم يبدو لي أن بإمكاني الإحساس بمشاعر إيجابية على الإطلاق. I couldn’t seem to experience any positive feeling at all. 0 1 2 3 شعرت بصعوبة في التنفس (شدة التنفس السريع، اللهثان بدون القيام بمجهود جسدي مثلًا). I experienced breathing difficulty (e.g., excessively rapid breathing, breathlessness in the absence of physical exertion). 0 1 2 3 وجدت صعوبة بأخذ المبادرة بعمل الأشياء. I found it difficult to work up the initiative to do things. 0 1 2 3 كنت أميل إلى ردة فعل مفرطة للظروف والأحداث. I tended to over-react to situations. 0 1 2 3 شعرت برجفة (باليدين مثلًا). I experienced trembling (e.g., in the hands). 0 1 2 3 شعرت بأنني أستهلك الكثير في الطاقة العصبية (شعرت بأنني أستهلك الكثير من قدرتي على تحمل التوتر العصبي). I felt that I was using a lot of nervous energy. 0 1 2 3 كنت خائفًا من مواقف قد أفقد فيها السيطرة على أعصابي واسبب إحراجًا لنفسي. I was worried about situations in which I might panic and make a fool of myself. 0 1 2 3 شعرت بأن ليس لدي أي شيء أتطلع إليه. I felt that I had nothing to look forward to. 0 1 2 3 شعرت بأنني مضطرب ومنزعج. I found myself getting agitated. 0 1 2 3 أجد صعوبة في الاسترخاء. I found it difficult to relax. 0 1 2 3 شعرت بالحزن والغم. I felt downhearted and blue. 0 1 2 3 كنت لا أستطع تحمل أي شيء يحول بيني وبين ما أرغب في القيام به. I was intolerant of anything that kept me from getting on with what I was doing. 0 1 2 3 شعرت بأنني على وشك الوقوع في حالة من الرعب المفاجئ بدون سبب. I felt I was close to panic. 0 1 2 3 فقدت الشعور بالحماس لأي شيء. I was unable to become enthusiastic about anything. 0 1 2 3 شعرت بأن قيمتي قليلة كشخص. I felt I wasn’t worth much as a person. 0 1 2 3 شعرت بأنني أميل إلى الغيظ بسرعة. I felt that I was rather touchy. 0 1 2 3 شعرت بضربات قلبي بدون مجهود جسدي (زيادة في معدل الدقات، أو غياب دقة قلب مثلًا). I was aware of the action of my heart in the absence of physical exertion (e.g., sense of heart rate increase, heart missing a beat). 0 1 2 3 شعرت بالخوف بدون أي سبب وجيه. I felt scared without any good reason. 0 1 2 3 شعرت بأن الحياة ليس لها معنى. I felt that life was meaningless. 0 1 2 3 Consent was obtained or waived by all participants in this study. Biomedical Research Ethics Committee, Umm Alqura University issued approval #HAPO-02-K-012-2023-02-1476 Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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